Variant 19-56664316-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001005850.3(ZNF835):c.883C>A(p.Gln295Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF835
NM_001005850.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.23

Variant links:

Genes affected

ZNF835 (HGNC:34332): (zinc finger protein 835) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF835 links:

ZIM2-AS1 (HGNC:):

ZIM2-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08948463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF835	NM_001005850.3 linkuse as main transcript	c.883C>A	p.Gln295Lys	missense_variant	2/2	ENST00000537055.4	NP_001005850.2	Q9Y2P0
ZNF835	XM_005259382.3 linkuse as main transcript	c.883C>A	p.Gln295Lys	missense_variant	2/2		XP_005259439.1	Q9Y2P0
ZNF835	XM_005259383.4 linkuse as main transcript	c.883C>A	p.Gln295Lys	missense_variant	2/2		XP_005259440.1	Q9Y2P0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF835	ENST00000537055.4 linkuse as main transcript	c.883C>A	p.Gln295Lys	missense_variant	2/2	2	NM_001005850.3	ENSP00000444747.1		Q9Y2P0
ZIM2-AS1	ENST00000650950.1 linkuse as main transcript	n.202-2961G>T		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000862

AC:

AN:

232012

Hom.:

AF XY:

0.00000792

AC XY:

AN XY:

126208

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000596

Gnomad SAS exome

AF:

0.0000339

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1453374

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722616

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2023

The c.883C>A (p.Q295K) alteration is located in exon 2 (coding exon 1) of the ZNF835 gene. This alteration results from a C to A substitution at nucleotide position 883, causing the glutamine (Q) at amino acid position 295 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.0048

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.52

M_CAP

Benign

0.0023

MetaRNN

Benign

0.089

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.060

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.4

REVEL

Benign

0.042

Sift

Benign

0.39

Sift4G

Benign

0.59

Vest4

0.036

MVP

0.20

ClinPred

0.20

GERP RS

2.1

Varity_R

0.12

gMVP

0.033

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over